IV: MEASLES VACCINE SAFETY AND EFFECTIVENESS

Friday, 24th of June 2011

MEASLES VACCINE SAFETY AND EFFECTIVENESS

Field Effectiveness of Live Attenuated Measles-Containing Vaccines: A Review of Published Literature

1. 1.   Amra Uzicanin and
2. 2.   Laura Zimmerman 

+ Author Affiliations

1. 1.    Centers for Disease Control and Prevention, Atlanta, Georgia
2. Correspondence: Amra Uzicanin, MD, MPH, Centers for Disease Control and Prevention, 1600 Clifton Rd, Mail Stop E-03, Atlanta, GA 30333 (aau5@cdc.gov).

Abstract

Background.  Information on measles vaccine  effectiveness (VE) is critical to help inform policies for future global measles control goals.

Methods. We reviewed results of VE studies  published during 1960–2010.

Results. Seventy papers with 135 VE point  estimates were identified. For a single dose of vaccine administered at 9–11 months of age and ≥12 months, the median VE was 77.0% (interquartile range [IQR], 62%–91%) and 92.0% (IQR, 86%–96%), respectively. When analysis was restricted to include only point estimates for which vaccination history was verified and cases were laboratory confirmed, the median VE was 84.0% (IQR, 72.0%–95.0%) and 92.5% (IQR, 84.8%–97.0%) when vaccine was received at 9–11 and ≥12 months, respectively. Published VE vary by World Health Organization region, with generally lower estimates in countries belonging to the African and SouthEast Asian Regions. For 2 doses of measles-containing vaccine, compared with no vaccination, the median VE was 94.1% (IQR, 88.3%–98.3%).

Conclusions. The VE of the first dose of  measles-containing vaccine administered at 9–11 months was lower than what would be expected from serologic evaluations but was higher than expected when administered at ≥12 months. The median VE increased in a subset of articles in which classification bias was reduced through verified vaccination history and laboratory confirmation. In general, 2 doses of measles-containing vaccine provided excellent protection against measles.

http://jid.oxfordjournals.org/content/204/suppl_1/S133.abstract

 

 

Persistence of Vaccine-Induced Measles Antibody Beyond Age 12 Months: A Comparison of Response to One and Two Doses of Edmonston-Zagreb Measles Vaccine Among HIV-Infected and Uninfected Children in Malawi

1. 1.   Ashley Fowlkes1,
2. 2.   Desiree Witte2,
3. 3.   Judy Beeler3,
4. 4.   Susette Audet3,
5. 5.   Philip Garcia1,
6. 6.   Aaron Curns1,
7. 7.   Chunfu Yang1,
8. 8.   Richard Fudzulani2,
9. 9.   Robin Broadhead2,

10. William J. Bellini1,

11. Felicity Cutts4 and

12. Rita F. Helfand1 

+ Author Affiliations

1. 1.    ¹Centers for Disease Control and Prevention, Atlanta, Georgia
2. 2.    ²College of Medicine, University of Malawi, Blantyre, Malawi
3. 3.    ³Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland
4. 4.    ⁴London School of Hygiene and Tropical Medicine, United Kingdom
5. Correspondence: Ashley Fowlkes, MPH, Centers for Disease Control and Prevention, 1600 Clifton Rd, NE MS A34, Atlanta, GA 30333 (afowlkes@cdc.gov).

Abstract

Background. Previously, we demonstrated that  measles antibody prevalence was lower at age 12 months among children infected with human immunodeficiency virus (HIV) than uninfected children following measles vaccination (MV) at ages 6 and 9 months. Among HIV-uninfected children, measles antibody prevalence was lower among 1- than 2-dose MV recipients. Here, we report results through age 24 months.

Methods.  Children born to HIV-infected  mothers received MV at 6 and 9 months, and children of HIV-uninfected mothers were randomized to MV at 6 and 9 months or MV at 9 months. We followed children through age 24 months. The child's HIV status was determined and measles immunoglobulin G (IgG) level was measured by enzyme immunoassay (EIA) and by plaque reduction neutralization (PRN) on a subset.

Results.  Among HIV-uninfected children, the  difference in measles antibody prevalence at age 12 months between one- and two-dose recipients reported previously by EIA was shown to be smaller by PRN. By age 24 months, 84% and 87% of HIV-uninfected children receiving 1 or 2 doses, respectively, were seroprotected. Only 41% of 22 HIV-infected children were measles seroprotected at age 20 months.

Discussion. Measles seroprotection persisted  through age 24 months among HIV-uninfected children who received 1 or 2 doses of MV. HIV-infected children demonstrated seroprotection through age 12 months, but this was not sustained.

http://jid.oxfordjournals.org/content/204/suppl_1/S149.abstract

 

International Measles Incidence and Immunization Coverage

1. 1.   Robert Hall and
2. 2.   Damien Jolley 

+ Author Affiliations

1. 1.    Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia
2. Correspondence: Robert Hall, MBBS MPH, School of Public Health and Preventive Medicine, Monash University, The Alfred Centre, 99 Commercial Rd, Melbourne, Victoria 3004, Australia (robert.hall@monash.edu).

Abstract

Measles is exquisitely sensitive to immunization programs. We investigated the decline in measles incidence after immunization with 1 or 2 doses of measles-containing vaccine (MCV), with or without supplementary immunization activities (SIAs). Using data from the World Health Organization, we modeled the impact of measles immunization using a negative binomial regression model. All countries offer measles immunization, and 192 of 193 countries offer a second dose of MCV (MCV2), using either a routine second dose, SIAs, or both. The incidence of measles fell from a median of 70.9 cases/100,000/year when coverage with a first dose of MCV (MCV1) was in the range of 0%–39% to a median of .9 cases/100,000/year when MCV1 coverage was 90%–100%, in both cases with no MCV2. Further reductions followed the introduction of MCV2 and SIAs. Modeling showed that each 1% increase in MCV1 coverage was followed by a 2.0% decrease in incidence in the same and following years (95% confidence interval [CI], 2.0%–1.9%, and 2.1%–1.9%, respectively). For a second dose, a rise of 1% in MCV2 coverage was followed by a decrease in measles incidence by .4% (95% CI, .3%–.5%) in the same year and .3% (95% CI, .2%–.5%) in the following year. SIAs were followed by decreases of measles incidence by 40.3% (95% CI, 46.3%–33.8%) in the same year and 45.2% (95% CI, 51.1%–48.7%) in the following year. A herd immunity effect was demonstrated with MCV1 coverage of >80%, and SIAs are an extraordinarily effective strategy for measles control.

http://jid.oxfordjournals.org/content/204/suppl_1/S158.abstract Expand+

 

Measles Vaccination in HIV-Infected Children: Systematic Review and Meta-Analysis of Safety and Immunogenicity

1. 1.   Pippa Scott1,
2. 2.   William J. Moss2,
3. 3.   Zunera Gilani2 and
4. 4.   Nicola Low1 

+ Author Affiliations

1. 1.    ¹Division of Clinical Epidemiology and Biostatistics, Institute of Social and Preventive Medicine, University of Bern, Switzerland
2. 2.    ²Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
3. Correspondence: Nicola Low, MD, MSc, FFPH, Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, Bern, CH-3012, Switzerland (low@ispm.unibe.ch.).

Abstract

Background.  Measles control may be more  challenging in regions with a high prevalence of HIV infection. HIV-infected children are likely to derive particular benefit from measles vaccines because of an increased risk of severe illness. However, HIV infection can impair vaccine effectiveness and may increase the risk of serious adverse events after receipt of live vaccines. We conducted a systematic review to assess the safety and immunogenicity of measles vaccine in HIV-infected children.

Methods. The authors searched 8 databases  through 12 February 2009 and reference lists. Study selection and data extraction were conducted in duplicate. Meta-analysis was conducted when appropriate.

Results. Thirty-nine studies published from  1987 through 2008 were included. In 19 studies with information about measles vaccine safety, more than half reported no serious adverse events. Among HIV-infected children, 59% (95% confidence intervals [CI], 46–71%) were seropositive after receiving standard-titer measles vaccine at 6 months (1 study), comparable to the proportion of seropositive HIV-infected children vaccinated at 9 (8 studies) and 12 months (10 studies). Among HIV-exposed but uninfected and HIV-unexposed children, the proportion of seropositive children increased with increasing age at vaccination. Fewer HIV-infected children were protected after vaccination at 12 months than HIV-exposed but uninfected children (relative risk, 0.61; 95% CI, .50–.73).

Conclusions. Measles vaccines appear to be  safe in HIV-infected children, but the evidence is limited. When the burden of measles is high, measles vaccination at 6 months of age is likely to benefit children of HIV-infected women, regardless of the child's HIV infection status.

http://jid.oxfordjournals.org/content/204/suppl_1/S164.abstract

 

 

Safety and Immunogenicity of Early Measles Vaccination in Children Born to HIV-Infected Mothers in the United States: Results of Pediatric AIDS Clinical Trials Group (PACTG) Protocol 225

1. 1.   Sulachni Chandwani1,
2. 2.   Judy Beeler2,
3. 3.   Hong Li3,
4. 4.   Susette Audet2,
5. 5.   Betsy Smith4,
6. 6.   John Moye5,
7. 7.   David Nalin6 and
8. 8.   Keith Krasinski1
9. 9.   for The PACTG 225 Study Team

+ Author Affiliations

1. 1.    ¹Department of Pediatrics, New York University School of Medicine, New York City
2. 2.    ²United States Food and Drug Administration, Bethesda, Maryland
3. 3.    ³Harvard School of Public Health, Cambridge, Massachusetts
4. 4.    ⁴National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
5. 5.    ⁵National Institute of Child Health & Human Development, Bethesda, Maryland
6. 6.    ⁶Former Director, Vaccine Scientific Affairs, Merck Vaccine Division (retired) West Point, Pennsylvania
7. Correspondence: Sulachni Chandwani, MD, Associate Professor of Pediatrics, NYU School of Medicine, 550 First Avenue, 8W46 NB Bldg. New York, NY 10016 (sulachni.chandwani@nyumc.org).

Abstract

Background.PACTG (Pediatric AIDS Clinical  Trials Group) 225, a multicenter, randomized, open-label trial in the United States evaluated reactogenicity and immunogenicity of 2 vaccination regimens: monovalent measles vaccine (Attenuvax) at 6 months of age and measles, mumps, and rubella, live attenuated (MMRII) vaccine at 12 months of age (2D), or only MMRII at 12 months of age (1D) in human immunodeficiency virus–infected (HIV-infected) (POS) and uninfected (NEG) children in the pre–highly active antiretroviral therapy (pre-HAART) period.

Methods. Plaque-reduction neutralization  (PRN) of measles-neutralizing antibody titers were evaluated at study weeks 0, 6, 26, 32, 52, and 130 (∼3 years of age).

Results.The 110 subjects included: 65  2DNEG; 30 1DNEG; 7 2DPOS and 8 1DPOS. Vaccinations (n = 175) were associated with no adverse experiences >Grade 2 except for Grade 3 fever (n = 2, 1 1DPOS and 1 1DNEG). Six weeks after Attenuvax, all 2DPOS subjects (7/7) seroresponded (PRN titers ≥120 mIU/mL) with median titers significantly exceeding 2DNEG titers (2115 vs 628 mIU/mL, respectively; P = .023). At ∼3 years of age, 67% 1DPOS (4/6) and 83% 2DPOS (4/5) subjects maintained titers ≥120 mIU/mL. Prevaccination titers ≥25 mIU/mL among 2DNEG subjects correlated inversely with the likelihood of achieving titers ≥120 mIU/mL (56% vs 90%; P = .004).

Conclusions. Among HIV-infected children  pre-HAART, Attenuvax at 6 months was well tolerated and immunogenic. These data support the current World Health Organization (WHO) recommendation to administer a first dose of measles vaccine at 6 months of age to HIV-infected children.

http://jid.oxfordjournals.org/content/204/suppl_1/S179.abstract

 

 

 

Measles Supplementary Immunization Activities and GAVI Funds as Catalysts for Improving Injection Safety in Africa

1. 1.   Edward J. Hoekstra1,
2. 2.   Maya M. V. X. van den Ent1,
3. 3.   Halima Dao1,
4. 4.   Hala Khalaf2 and
5. 5.   Annika Salovaara2 

+ Author Affiliations

1. 1.    ¹United Nations Children's Fund (UNICEF) Program Division, Health Section, New York, New York
2. 2.    ²UNICEF Supply Division, Copenhagen, Denmark
3. Correspondence: Edward John Hoekstra, MD, MSc, UNICEF Headquarters, 3 UN Plaza, New York, NY 10017 (ehoekstra@unicef.org).

Abstract

Background. In 2000, reuse of disposable  syringes and inadequately sterilized syringes resulted in 39% of all injections being unsafe, causing 22 million infections. We describe the contribution of measles supplemental immunization activities (SIAs) and Global Alliance for Vaccines and Immunisation (GAVI) funding in replacing disposable and sterilizable syringes with auto-disable (AD) syringes to improve injection safety in 39 African countries.

Methods. We assessed trends in nationwide  introduction of AD syringes against measles catch-up SIAs and GAVI funding using World Health Organization/United Nations Children's Fund (UNICEF) Joint Reporting Form for Immunization and UNICEF supply data.

Results. In 19 (49%) of 39 countries, the  measles program catalyzed the introduction of injection safety equipment, including AD syringes and safety boxes, training, and procurement of safety equipment during SIAs. GAVI was catalytic through financial support in 14 countries (36%) for including safe injection equipment in routine immunization. Additionally, GAVI funded 21 countries that had already introduced AD syringes in their national program. UNICEF AD syringe shipments to sub-Saharan Africa increased from 11 million to 461 million from 1997 to 2008. All 39 countries stopped using sterilizable syringes by 2004.

Conclusions. The measles mortality reduction  program and GAVI complemented each other in improving injection safety. All countries continued with AD syringes for immunization after measles catch-up SIAs and GAVI funding ended.

http://jid.oxfordjournals.org/content/204/suppl_1/S190.abstract